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Episode 2 14.03.2013
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How does a mouse nose with 1,200 receptor genes wire itself into a precise sensory map, and why is that map less stereotyped than we once believed? Peter Mombaerts explores the genetics and development of olfactory circuit formation.
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Peter Mombaerts describes the remarkable complexity of the mouse olfactory system, where approximately 1,200 odorant receptor genes each expressed by a distinct population of sensory neurons must organize their axonal projections into roughly 3,600 glomeruli in the olfactory bulb. Using gene targeting and molecular labeling techniques, his laboratory has spent two decades investigating how this glomerular map develops and what role the receptor proteins themselves play in axon guidance and glomerular identity.
A central theme is the surprising degree of variability in glomerular positioning. Mombaerts challenges the widely used term “stereotyped” to describe the glomerular map, demonstrating that even between the left and right bulbs of the same inbred mouse, the relative positions of identified glomeruli can be inverted. He prefers terms like “recognizable” or “reproducible,” noting that the precision is insufficient to construct a definitive atlas as has been done for Drosophila. This variability has important implications for understanding the mechanisms of map formation: if the map were truly stereotyped, extremely complex molecular guidance mechanisms would be required, but acknowledging the jitter relaxes these demands considerably.
The conversation explores the genomic organization of odorant receptor genes, which Mombaerts describes as “haphazard,” distributed across approximately 40 loci with the largest cluster containing around 300 genes. Expression levels vary over two orders of magnitude between different receptor types, and the one-neuron-one-receptor rule, while strongly supported, remains an asymptotic conclusion. Remarkably, replacing an odorant receptor’s coding region with the beta-2 adrenergic receptor still produces neurons that form a recognizable glomerulus and respond to appropriate ligands, suggesting that the receptor protein’s role in axon guidance may not be unique to olfactory receptors.
The episode also addresses the emerging recognition that odorant receptor genes are expressed outside the nose, including in kidneys where knockout of one receptor affects blood pressure regulation, hinting at broader biological roles for this gene family beyond olfaction.
Tagged as:
Genes Expressed Glomerular Mouse Odorant Receptor odorant receptor genes Olfactory olfactory system Receptor Genes
About the author call_made
Both the triumphs of humanity and its most evil deeds have resulted from collaboration. In a time where humanity is required to aspire to the former and minimize the latter, the question arises of how collaboration arises and why it fails. Surprisingly, this phenomenon, so central to who we are, is not well understood. Hence, a collaborative effort is required to understand collaboration in its full biological, psychological, sociological, cultural, and economic complexity and to translate this understanding into operational impact. This series of podcasts is one step toward achieving these complementary goals. The Collaboration Podcast presents interviews with people who are central orchestrators of collaboration in various domains including business, government, science, art, health, sustainability, and the military. The discussions were conducted by Prof. Dr. Paul F.M.J. Verschure and members of the Program Advisory Committee of the Ernst Strungmann Forum on Collaboration (https://www.esforum.de/forums/ESF32_Collaboration.html) during 2021 and had the goal to sketch a map of opportunities, challenges, and obstacles in human collaboration. The forum took place in May 2022, and now we would like to share this series of interviews with a broader audience. The full report of the Forum will be published in 2023 by MIT Press. The podcast was produced by the Convergent Science Network (https://www.convergentsciencenetwork.org/). Context: The stability of social systems depends critically on realizing sustainable methods of “collaboration,” yet how and by which means collaboration is achieved is not clearly understood; neither are the conditions or processes that lead to its breakdown or failure. Collaboration can be understood as cooperation between agents toward mutually constructed goals. Part of the reason for our lack of understanding is that the phenomenon of collaboration is, by nature, a highly multidisciplinary problem, and effective research into its complexities has been difficult to achieve across the broad range of scientific and technical disciplines involved. The need for a fundamental understanding of collaboration, however, has become increasingly important. Not only does humankind demand answers as it attempts to address critical challenges at multiple scales (e.g., climate change, migration, enhanced automation, social and economic inequality), but ever-increasing technological and economic means of interconnecting people and societies are disrupting long-established, familiar patterns of how we interact. Radical technological changes that are ongoing have the potential to reshape collaboration in ways that are currently hard to predict or influence (e.g., by altering configurations in interaction, information creation, and modes of communication). On one hand, such changes could disrupt hitherto stable forms of collaboration by affecting critical communication channels and traditional roles, as can be observed in the rapidly changing patterns in governance, commerce, and social interaction. Conversely, technology could lead to the emergence of novel, successful forms of collaboration that deviate from traditional “hierarchical” architectures. Evidence of this can be seen in areas as diverse as highly automated manufacturing plants, the open science movement, collaborative software repositories, user-centered services, and the sharing of economy-based modes of organization. Without a fundamental understanding of the mechanisms, processes, and boundary conditions of collaboration, it is not possible to evaluate or predict which of these possible scenarios are sustainable or even plausible. The Forum “How Collaboration Arises and Why it Fails” (May 8–13, 2022, Location: Frankfurt am Main, Germany) Chairs: Andreas Roepstorff and Paul Verschure Program Advisory Committee: Jenna Bednar, Julia R. Lupp, Bhavani R. Rao , Andreas Roepstorff, Ferdinand von Siemens, and Paul Verschure
15.03.2013
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